The structural and functional relationshp between nerve growth factor (NGF) and insulin, previously described, will continue to be explored through several approaches. Chemical modification experiments will be expanded to include lysine, arginine and histidine residues which will be investigated for their role in the biological activity of NGF and their topographical location in the three-dimensional structure. These studies will also be carried out on snake venom NGF (Naja naja) and results compared to the mouse protein. Sequence analysis of this protein will be completed. The biosynthesis of NGF will be explored in detail. The studies indicating glioblastoma cells as a source will be expanded to normal glia. In addition, the product of this synthesis, which appears to be a somewhat larger version of NGF, will be characterized in detail. Molecular properties, sequence analysis and biological characterization will be performed. Other organs will also be tested for their ability to synthesize NGF (or pre NGF) in cell-free systems. The expanding view that NGF exerts positive effects in the central nervous system will be explored. Characterization of the binding, including isolation of the receptor, and determination of possible effects on the metabolism or specific enzyme induction will be explored. Similarly studies will be carried out to determine the properties and significance of the specific binding found in peripheral end organs. Finally, the post-receptor mechanism will be studied with particular reference to the role of calcium in axon proliferation and cell stabilization.